Amphiphilic polymers having both hydrophobicity and hydrophilicity have been of interest. Particularly, amphiphilic polymers that exhibit a temperature-sensitive sol-gel behavior are now studied intensively in the drug delivery system and medical fields, and studies on their use are also actively conducted. Particularly, copolymers composed of polyethylene oxide and polypropylene oxide are commercially available under the trade names Pluronic and Poloxamer and used in various applications.
However, the Pluronic- and Poloxamer-based polymers encountered problems upon use in medical applications due to non-biodegradability. For this reason, copolymers composed of biodegradable polylactide (PLA) (or polyglycolide (PGA), polycaprolactone (PCL) and a copolymer thereof) and polyethylene glycol (PEG) have been studied and used.
U.S. Pat. Nos. 4,882,168 and 4,716,203 disclose copolymers of hydrophilic polyalkylene glycol with polyglycolic acid, trimethylene carbonate and the like.
Furthermore, U.S. Pat. No. 4,942,035 discloses a pharmaceutical composition comprising a block copolymer of polyethylene glycol (PEG) with polylactide (PLA), polyglycolide (PGA), polycaprolactone (PCL), hydrophobic polypeptide or polyacetal.
Moreover, U.S. Pat. No. 5,476,909 discloses a biodegradable triblock (A-B-A) copolymer consisting of: hydrophobic blocks (A) comprising polylactide (PLA), polyglycolide (PGA) or derivatives thereof, and a hydrophilic block (B) comprising polyethylene glycol (PEG) or its derivatives.
And, U.S. Pat. No. 5,548,035 discloses a biodegradable multi-block copolymer with thermoplasticity comprising a hydrophobic block selected from polylactide, polyglycolic acid, a copolymer thereof, and polycaprolactone.
Meanwhile, Korean Patent Laid-Open Publication No. 2000-0012970 (Mar. 6, 2000) discloses a pH-sensitive polymer comprising sulfonamide groups, and a preparation method thereof. This patent relates mainly to either a change in the solubility of linear polymers formed by the random copolymerization of sulfonamide monomers with DMAAm or NiPAAm, or the swelling index of crosslinked polymers thereof.
The above-described prior arts were so designed that a sol-gel transition phenomenon is shown by the use of the block copolymer of the hydrophobic biodegradable polymer with the hydrophilic polymer. The block copolymer when injected in vivo in an aqueous solution form, a sol state, is changed into a gel state. Thus, the block copolymer was used as a sustained-release drug delivery system which carries and slowly releases drugs in vivo.
However, block copolymers that exhibit a temperature sensitive sol-gel transition phenomenon cause problems, such as the clogging phenomenon of injection needles occurring during injection before in vivo injection, since in vivo temperature and the temperature of the injection needles are adjusted to the same temperature by thermal equilibrium. In addition, hydrophobic moieties comprised of PLA, PLGA or PCL are reported to exhibit pH sensitivity. However, such moieties are not so sensitive that they can be applied to in vivo pH, and thus, they are not suitable for practical use in the drug delivery field.